The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, preliminary anti-tumor activity, and to determine the recommended Phase II dose (RP2D) of the ALE.P02 monotherapy in adult patients with selected squamous solid tumors.
This Study has a Phase I ALE.P02 monotherapy dose escalation and recommended dose for expansion (RDE) study and a Phase II study of ALE.P02 as monotherapy at RP2D in adult patients with selected advanced or metastatic Claudin-1 positive (CLDN1+) cancers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
170
ALE.P02, will be administered by IV infusion according to the assigned arms.
Mayo Foundation for Medical Education and Research - Mayo Cl
Scottsdale, Arizona, United States
RECRUITINGProvidence Medical Foundation
Fullerton, California, United States
RECRUITINGUSC Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGYale Comprehensive Cancer Center
New Haven, Connecticut, United States
Number of Patients with Dose Limiting Toxicities (DLTs)
DLTs as defines in the protocol will be assessed to evaluate safety and tolerability of ALE.P02 (Phase I Dose Escalation), and to establish RP2D for ALE.P02 (Phase I RDE).
Time frame: Up to 28 days
Number of Patients with Adverse Events
Adverse events will be assessed to evaluate safety and tolerability of ALE.P02 (Phase I Dose Escalation), and to establish RP2D for ALE.P02 (Phase I RDE).
Time frame: Screening (day -28 to day -1) up to Safety follow-up (30 ± 5 days post last dose [Up to 3.5 years])
Overall Response Rate (ORR) (Phase I)
The ORR is the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.) This is assessed to establish RP2D for ALE.P02 (Phase I RDE)
Time frame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
Duration of Response (DoR) (Phase I)
The DoR is defined for patients achieving a confirmed CR or PR as the time from the initial response of CR or PR per Investigator review according to RECIST 1.1 to disease progression or death of any cause, whichever occurs earlier. This is assessed to establish RP2D for ALE.P02 (Phase I RDE).
Time frame: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)
Overall Response Rate (ORR) (Phase II)
The ORR is assessed to assess anti-tumor activity of ALE.P02 (Phase II).
Time frame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
Duration of Response (DoR) (Phase II)
The DoR is assessed to assess anti-tumor activity of ALE.P02 (Phase II).
Time frame: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)
Disease control rate (DCR) (Phase I and II)
The DCR is defined as the proportion of patients with a confirmed BOR of CR or PR or stable disease (SD) per Investigator review according to RECIST 1.1 at or prior to initiation of the use of new anti-cancer therapy. This is assessed to evaluate preliminary evidence of anti-tumor activity of ALE.P02 (Phase I and II).
Time frame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
Median Progression-Free Survival (PFS) at 6 and 12 Months (Phase I and II)
The PFS is defined as time from first study treatment to a documented disease progression according to RECIST 1.1, as determined by the Investigator, or death due to any cause, whichever occurs earlier. This is assessed to evaluate preliminary evidence of anti-tumor activity of ALE.P02 (Phase I and II).
Time frame: At 6 and 12 months after initiation of ALE.P02 treatment
Median Overall Survival (OS) at 6, 12, and 24 Months (Phase I and II)
The OS is defined as time from first study treatment to death due to any cause. This is assessed to evaluate preliminary evidence of anti-tumor activity of ALE.P02 (Phase I and II).
Time frame: At 6, 12, and 24 months after initiation of ALE.P02 treatment
Blood Concentration of ALE.P02 Antibody-drug Conjugate (ADC)
Concentrations of ALE.P02 ADC in blood will be measured at each scheduled time point per arms to assess the pharmacokinetic (PK) profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at end of treatment visit (EoT) (Up to 3.5 years)
Blood Concentration of Total Antibody
Total antibody in blood will be measured at each scheduled time point per arms to assess the PK profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Blood Concentrations of Payload
Concentrations of payload in blood will be measured at each scheduled time point per arms to assess the PK profile of ALE.P02.
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The University of Chicago Medical Center - Oncology
Chicago, Illinois, United States
RECRUITINGNorton Cancer Institue Downtown
Louisville, Kentucky, United States
RECRUITINGHackensack University Medical Center
Hackensack, New Jersey, United States
RECRUITINGNEXT Oncology Virginia
Fairfax, Virginia, United States
RECRUITINGInstitut Bergonie
Bordeaux, France
RECRUITINGCentre Georges Francois Leclerc - Oncologie Medicale
Dijon, France
RECRUITING...and 28 more locations
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Area under the concentration-time curve over the dosing interval (AUCtau)
The AUCtau of ALE.P02 will be measured to assess the pharmacokinetic (PK) profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration (AUClast)
The AUClast of ALE.P02 will be measured to assess the PK profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf)
The AUCinf of ALE.P02 will be measured to assess the PK profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Maximum Concentration (Cmax)
The Cmax of ALE.P02 will be measured to assess the PK profile of ALE.P02. It is determined directly from the concentration-time profile.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Minimum concentration (Cmin)
The Cmin of ALE.P02 will be measured to assess the PK profile of ALE.P02. It is determined directly from the concentration-time profile.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Concentration at the end of a Dosing Interval (Ctrough)
The Ctrough of ALE.P02 will be measured to assess the PK profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
The terminal elimination rate constant (KeL)
The KeL of ALE.P02 will be measured to assess the PK profile of ALE.P02. It is determined by selection of at least three data points on the terminal phase of the concentration-time curve.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Terminal elimination half-life (t½)
The t½ of ALE.P02 will be measured to assess the PK profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Time of Maximum Concentration (tmax)
The tmax of ALE.P02 will be measured to assess the PK profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Average Concentration (Cavg)
The Cavg of ALE.P02 will be measured to assess the PK profile of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Number of Patients with Presence of anti-ALE.P02 Antibodies
Presence of anti-ALE.P02 Antibodies will be assessed to evaluate the immunogenicity of ALE.P02.
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)